Objective: Inherited myopathies are a diverse group of genetic muscle disorders characterized by muscle weakness and dysfunction resulting from mutations in genes with a wide range of biological functions. This study was performed to elucidate genetic causes in a large family with late-onset myofibrillar myopathy. Methods: Whole-exome sequencing was first applied to the proband, and then subsequent filtering process and in silico analysis was performed to determine causative mutation. Results: This study identified an unreported likely pathogenic mutation, p.Met160Ile, in the LIM domain binding 3 (LDB3) gene. This missense mutation showed complete cosegregation with affected individuals and was located at an evolutionarily well-conserved site. Several in silico analyses, along with simulations of three-dimensional structural changes in the mutant protein, predicted its potential pathogenicity. Conclusion These findings expand the current understanding of the genetic basis of inherited myopathy and underscore the importance of comprehensive genetic analysis in clinical practice.